Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 2

NCT01956123 | Completed Phase 3 Results

• 3 other identifiers: 0000712013-001616-30U1111-1147-6922
• Study Type: interventional
• Target: 513
• Locations: 11 countries
• Sites: 13

Brief Summary

This trial investigates the immunogenicity of FE 999049 in repeated cycles.

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

• Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles

  The proportion (percentage) of participants with at least one treatment-induced anti-FSH antibody response at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once.

  Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose

Secondary Outcomes (11)

• Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles

  Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose

• Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles

  Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose

• Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle

  ≤9 days after triggering of final follicular maturation.

• Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle

  End-of-stimulation (up to 20 stimulation days)

• Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle

  5-6 weeks after blastocyst transfer

Study Arms (4)

A

EXPERIMENTAL

Follitropin Delta (FE 999049) (COS cycle 2)

Drug: Follitropin Delta (FE 999049)

B

ACTIVE COMPARATOR

Follitropin Alfa (GONAL-F) (COS cycle 2)

Drug: Follitropin Alfa (GONAL-F)

C

EXPERIMENTAL

Follitropin Delta (FE 999049) (COS cycle 3)

Drug: Follitropin Delta (FE 999049)

D

ACTIVE COMPARATOR

Follitropin Alfa (GONAL-F) (COS cycle 3)

Drug: Follitropin Alfa (GONAL-F)

Interventions

Follitropin Delta (FE 999049) DRUG

A; C

Follitropin Alfa (GONAL-F) DRUG

B; D

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed Consent Documents signed prior to screening evaluations related to this protocol
• Participation in the pivotal efficacy trial (trial 000004/ESTHER-1)
• Anti-FSH antibody results from baseline and at least one post-dosing assessment in the previous cycle(s) available.
• Having undergone the oocyte retrieval procedure, or having had cycle cancellation prior to oocyte retrieval due to poor ovarian response or excessive ovarian response, in the previous cycle(s).
• Failure to achieve ongoing pregnancy in the previous cycle(s).

You may not qualify if:

• Non-compliance to protocol compliance in the previous cycle(s).
• Having undergone any stimulation with gonadotropins since the end-of-trial / end-of-cycle visit in the previous cycle
• One or more follicles ≥10 mm observed on the transvaginal ultrasound prior to start of dosing on stimulation day 1
• Severe OHSS in a previous cycle.
• Any clinically relevant change to any of the eligibility criteria in the previous cycle(s).
• Clinically relevant medical history since the previous cycle which precludes gonadotropin stimulation or is associated with a reduced chance of pregnancy.

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (13)

UZ Brussel (there may be other sites in this country)

Brussels, Belgium

Location

Fertilitat and PUC-RS (there may be other sites in this country)

Porto Alegre, Brazil

Location

Pacific Centre for Reproductive Medicine

Burnaby, British Columbia, Canada

Location

Olive Fertility Centre

Vancouver, British Columbia, Canada

Location

Ottawa Fertility Centre

Ottawa, Ontario, Canada

Location

IVF CUBE SE (there may be other sites in this country)

Prague, Czechia

Location

Rigshospitalet Fertilitetsklinikken (there may be other sites in this country)

Copenhagen, Denmark

Location

Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre (there may be other sites in this country)

Lille, France

Location

Centro Natalità San Raffaele (there may be other sites in this country)

Milan, Italy

Location

The nOvum Clinic (there may be other sites in this country)

Warsaw, Poland

Location

IVF & Reproductive Genetics Center (there may be other sites in this country)

Moscow, Russia

Location

IVI Sevilla (there may be other sites in this country)

Seville, Spain

Location

Glasgow Centre for Reproductive Medicine Ltd. (there may be other sites in this country)

Glasgow, United Kingdom

Location

Related Publications (3)

• Havelock J, Aaris Henningsen AK, Mannaerts B, Arce JC; ESTHER-1 and ESTHER-2 Trial Groups. Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta. J Assist Reprod Genet. 2021 Oct;38(10):2651-2661. doi: 10.1007/s10815-021-02271-5. Epub 2021 Jul 13.

  PMID: 34254211 RESULT

• Fernandez-Sanchez M, Fatemi H, Garcia-Velasco JA, Heiser PW, Daftary GS, Mannaerts B. Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach. Gynecol Endocrinol. 2023 Dec;39(1):2205952. doi: 10.1080/09513590.2023.2205952.

  PMID: 37156263 RESULT

• Nelson SM, Larsson P, Mannaerts BMJL, Nyboe Andersen A, Fauser BCJM. Anti-Mullerian hormone variability and its implications for the number of oocytes retrieved following individualized dosing with follitropin delta. Clin Endocrinol (Oxf). 2019 May;90(5):719-726. doi: 10.1111/cen.13956. Epub 2019 Mar 18.

  PMID: 30801744 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

follitropin delta; FE 999049; follitropin alfa

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Results Point of Contact

• Title: Global Clinical Compliance
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Clinical Development Support

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2013
• First Posted: October 8, 2013
• Study Start: March 26, 2014
• Primary Completion: May 1, 2015
• Study Completion: January 3, 2017
• Last Updated: September 6, 2023
• Results First Posted: September 21, 2018

Record last verified: 2018-08

Locations

DK (1); BR (1); FR (1); ES (1); CA (3); IT (1); BE (1); RU (1); CZ (1); GB (1); PL (1)